1u5s Citations

Structure of an ultraweak protein-protein complex and its crucial role in regulation of cell morphology and motility.

Mol. Cell 17 513-23 (2005)
Cited: 81 times
EuropePMC logo PMID: 15721255

Abstract

Weak protein-protein interactions (PPIs) (K(D) > 10(-6) M) are critical determinants of many biological processes. However, in contrast to a large growing number of well-characterized, strong PPIs, the weak PPIs, especially those with K(D) > 10(-4) M, are poorly explored. Genome wide, there exist few 3D structures of weak PPIs with K(D) > 10(-4) M, and none with K(D) > 10(-3) M. Here, we report the NMR structure of an extremely weak focal adhesion complex (K(D) approximately 3 x 10(-3) M) between Nck-2 SH3 domain and PINCH-1 LIM4 domain. The structure exhibits a remarkably small and polar interface with distinct binding modes for both SH3 and LIM domains. Such an interface suggests a transient Nck-2/PINCH-1 association process that may trigger rapid focal adhesion turnover during integrin signaling. Genetic rescue experiments demonstrate that this interface is indeed involved in mediating cell shape change and migration. Together, the data provide a molecular basis for an ultraweak PPI in regulating focal adhesion dynamics during integrin signaling.

Articles - 1u5s mentioned but not cited (1)

  1. CARDIO-PRED: an in silico tool for predicting cardiovascular-disorder associated proteins. Jain P, Thukral N, Gahlot LK, Hasija Y. Syst Synth Biol 9 55-66 (2015)


Reviews citing this publication (38)

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  30. Ultra-weak reversible protein-protein interactions. Rowe AJ. Methods 54 157-166 (2011)
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  34. Signalling via integrins: implications for cell survival and anticancer strategies. Hehlgans S, Haase M, Cordes N. Biochim. Biophys. Acta 1775 163-180 (2007)
  35. Weak protein-protein interactions as probed by NMR spectroscopy. Vaynberg J, Qin J. Trends Biotechnol. 24 22-27 (2006)
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  37. The parvins. Sepulveda JL, Wu C. Cell. Mol. Life Sci. 63 25-35 (2006)
  38. NMR analysis of protein interactions. Bonvin AM, Boelens R, Kaptein R. Curr Opin Chem Biol 9 501-508 (2005)

Articles citing this publication (42)

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